This proposal will examine the relationship of immunoregulatory immune cell phenotype and function to the development, clinical activity and disease sequellae of hypersensitivity pneumonitis in human and in a nonhuman primate model of the disease. One aspect of these studies will involve a comparison of in vitro immunologic reactivity (mitogen and antigen responsiveness) as well as immunoregulatory cell phenotype (FCGamma, T4, T8) and function using autologous cocultures in the peripheral blood and bronchial lavage fluids of symptomatic pigeon breeders, asymptomatic but equally exposed breeders and controls. In addition, after development of the Rhesus model, we will perform similar in vitro comparative studies in both symptomatic and asymptomatic but exposed monkeys. A second part of this proposal will examine the relationship of immunoegulatory cell imbalances in vitro and in vivo to disease development and activity using a combination of natural infection and abrogation of T (TBI and/or cimetidine) and prostaglandin mediated monocyte (indomethacin) suppressor cell function. In addition, we will examine the relationship of immunoregulatory imbalances (in vitro and in vivo) and the development of fibrosis (in vivo) using long-term abrogation of suppressor cell function (cimetidine and/or indocin) in conjunction with prolonged daily antigen expsoure. These studies, then, will provide correlative (human and monkey) and direct (monkey) evidence of the relationship between altered immunoregulation andn disease development, activity and sequellae of hypersensitivity pneumonitis in general and may have import for our understanding of other pulmonary inflammatory diseases.